Hyperglycolysis in endothelial cells drives endothelial injury and microvascular alterations in peritoneal dialysis.

ABSTRACT:

Background

Endothelial cell (EC) dysfunction leading to microvascular alterations is a hallmark of technique failure in peritoneal dialysis (PD). However, the mechanisms underlying EC dysfunction in PD are poorly defined.

Methods

We combined RNA sequencing with metabolite set analysis to characterize the metabolic profile of peritoneal ECs from a mouse model of PD. This was combined with EC-selective blockade of glycolysis by genetic or pharmacological inhibition of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) in vivo and in vitro. We also investigated the association between peritoneal EC glycolysis and microvascular alterations in human peritoneal samples from patients with end-stage kidney disease (ESKD).

Results

In a mouse model of PD, peritoneal

SUBMITTER: Si Z 

PROVIDER: S-EPMC10689974 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature